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Cardiotoxic and possible leukemogenic effects of adriamycin in nonhuman primates
Abstract:
10 monkeys (macaques) received adriamycin by monthly intravenous injections at 12 mg/m2 (1 mg/kg). 8 of the 10 monkeys developed congestive heart failure at an average cumulative adriamycin dose (310 mg/m2) well below that considered the safe upper limit (550 mg/m2) in man. Histologically, the myocardial lesions resembled those found in human anthracycline-induced cardiomyopathy. 1 of the 10 monkeys developed acute myeloblastic leukemia after receiving 324 mg/m2 of adriamycin; the 10th monkey is alive and well 26 months after the last dose of drug. Our results suggest that adriamycin is a more potent cardiotoxin in monkeys than in man, and that leukemia may be a consequence of prolonged treatment with this drug.
Insights
Adriamycin (adriamycin) is a potent cardiotoxin in monkeys, causing heart failure at lower doses than in humans. Prolonged adriamycin treatment may also lead to leukemia.
Area of Science:
- Cardiology
- Oncology
- Toxicology
Background:
- Adriamycin (doxorubicin) is a widely used chemotherapy agent.
- Anthracycline-induced cardiomyopathy is a known adverse effect in humans.
Purpose of the Study:
- To investigate the cardiotoxic and potentially leukemogenic effects of adriamycin in a non-human primate model.
- To compare adriamycin's toxicity in monkeys to established human safety limits.
Main Methods:
- Ten macaques received monthly intravenous injections of adriamycin (12 mg/m2).
- Monkeys were monitored for clinical signs of heart failure and histological changes.
- Cumulative doses were recorded to assess toxicity thresholds.
Main Results:
- Eight out of ten monkeys developed congestive heart failure at a mean cumulative dose of 310 mg/m2.
- Histological examination revealed myocardial lesions similar to human anthracycline-induced cardiomyopathy.
- One monkey developed acute myeloblastic leukemia after a cumulative dose of 324 mg/m2.
Conclusions:
- Adriamycin demonstrates greater cardiotoxicity in macaques than in humans.
- Prolonged adriamycin administration may be associated with an increased risk of secondary leukemia.